Engineered Multivariate Metal-Organic Frameworks for Magnetic Resonance Molecular Imaging Signal Enhancement

Trapping Xe atoms within MOFs represents a promising strategy for hyperpolarized 129Xe MRI, owing to their structural tunability and ultrahigh porosity. Enhancing the entrapped 129Xe NMR signal is critical to overcoming current limitations of 129Xe MRI in biomedical applications. Although metal-centered doping has been explored to boost 129Xe signals, ligand-centered precise engineering to optimize the entrapped 129Xe NMR signal in MOFs remains largely underexplored. Herein, we present, for the first time, a ligand-based multivariate engineering approach to enhance the entrapped 129Xe NMR signal of water-stable CAU-1-derived MTV-MOFs. By finely tuning the molar ratio of −OH and −NH2 functionalized linkers, the pore microenvironment and Xe-framework interactions are continuously modulated. The MTV-MOF with the optimal ligand composition exhibits a remarkable 65-fold enhancement in 129Xe NMR signal compared to the single-component MOF. Furthermore, this material demonstrates excellent 129Xe MRI performance in living cells, highlighting its potential for biomedical imaging. This ligand-engineered multivariate approach establishes a versatile platform for tailoring Xe-host interactions in MOFs, offering a promising pathway to develop high-performance Xe molecular cages and expand the frontier of MOF-based molecular imaging technologies.